Breast cancer is the second leading cause of cancer death in American women, with over 39,000 women dying of breast cancer yearly. Breast cancer diagnosis and treatment cause psychosocial distress, disrupted social relationships, anxiety, poor sleep, uncertainty, and fear of cancer recurrence. This distress can extend beyond treatment and adversely affect health-related quality of life (HRQOL). Interventions that stem the tide of negative emotions and their physiological sequelae are needed. Psychoneuroimmunology (PNI) has established that psychosocial distress impairs immune function. We have shown that women diagnosed with breast cancer have significant psychosocial distress that is accompanied by dysregulated natural killer cell activity (NKCA) and cytokine production. These observations are especially important in that impairment of these forms of immune function is associated with increased tumor initiation, primary tumor growth and tumor metastasis. Metastatic disease is the primary cause of death from breast cancer. Mindfulness based stress reduction (MBSR) is a mind-body intervention that shows promise for management of the distress associated with cancer. We show that MBSR reduces neuroendocrine stress activation and improves immune function and quality of life of breast cancer patients during the vulnerable period of cancer diagnosis and treatment. Using a randomized controlled design, this study will evaluate the potential benefits of MBSR on psychosocial distress, neuroendocrine stress activation, immune function, and HRQOL. Women with early stage breast cancer will be randomized to an 8-week MBSR intervention or a control condition. Assessments of immune function (NKCA and cytokines), neuroendocrine activity (salivary cortisol and plasma catecholamines), psychosocial response, and HRQL will be obtained pre-, mid-, at completion, and post-MBSR. Hypotheses will test whether MBSR can improve the psychosocial response of women to breast cancer diagnosis and treatment, reduce neuroendocrine stress activation, restore immune function, and increase HRQOL. The relationship among main study variables will be explored by mediation model testing. These assessments will be achieved during the critical period of cancer diagnosis and treatment when restoration of immune function is most significant. Understanding the trajectory and the nature of the psycho-endocrine-immune response to a promising mind-body approach like MBSR, using a rigorous design in a well-defined cancer population, will significantly contribute to the science of PNI and to integrative cancer care. PUBLIC HEALTH RELEVANCE: Alternative or complementary approaches that enhance the quality of life of women with breast cancer have grown in popularity. Yet, there is a lack of empirical analysis of such approaches using rigorous scientific design. The proposed study will so evaluate one such approach, mindfulness based stress reduction, in a population of women with breast cancer and in comparison to a matched group of women without cancer.